rs10512263

Positions:

• chr9-99123789-T-C
• chr9-99123789-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004612.4(TGFBR1):​c.98-5066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,246 control chromosomes in the GnomAD database, including 471 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (471 hom., cov: 32)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR1	NM_004612.4	c.98-5066T>C		intron_variant		ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9	c.98-5066T>C		intron_variant		1	NM_004612.4	P4

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10347 AN: 152128 Hom.: 473 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0680 AC: 10347 AN: 152246 Hom.: 471 Cov.: 32 AF XY: 0.0707 AC XY: 5262 AN XY: 74434

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0730 Hom.: 848

Bravo AF: 0.0702

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10512263; hg19: chr9-101886071;